Recent advances in the treatment and monitoring of HIV-1 infection have substantially diminished HIV-associated illness and mortality; however the management of HIV-infected patients has become increasingly complex. We are conducting studies that: characterize the immune recovery in persons with advanced HIV infection, including studies of discontinuation of prophylaxis against opportunistic infections; evaluate the management of antiretoviral therapy in individuals with advanced infection; and determine the HIV replication kinetics after interruption of successful anti-retroviral therapy. In a group of patients with inactive CMV retinitis, we demonstrated the safety of discontinuing anti-CMV maintenance therapy after HAART-induced increases in CD4+ T cell counts were observed. Immune recovery vitreitis occurred in this setting, possibly as a result of enhanced immune responses from HAART. We continue to monitor these patients for the durability of the enhanced immune response and associated problems. In addition, mathematical modeling of HIV viral load kinetics in a group of HIV-infected persons who were naive to therapy and were subsequently treated suggests that HIV continues to disseminate in spite of apparent control of HIV in the plasma. A metanalysis of persons receiving potent antiretroviral therapy suggested that it is possible to predict the long term response of antiretroviral therapy based on the initial response of the level of HIV in the plasma. Similar analyses of trials of treatment of Hepatitis C in persons coinfected with HIV and Hepatitis C suggest that it may be possible to predict long term response to anti-Hepatitis C therapy bassed on the initial response of the level of HCV in the plasma. Using combination therapy of pegylated interferon together with ribavirin in these subjects, we are determining whether the additional use of the growth factors erythropoietin and granulocyte colony stimulating factor to maintain dosing of the therapy can result in an improved therapeutic response in these coinfected patients. Another trial will determine whether prolonged use of pegylated interferon after standard therapy with pegylated interfereon and ribavirin can enhance the response to Hepatitis C therapy in persons with Hepatitis C infection and HIV infection. We continue to develop a database designed to capture clinical and laboratory data for the dual purposes of rapid access to data for patient care and research use. We continue our efforts to improve access to clinical trials by local minority populations through an outreach program that includes a close relationship with local clinics for the medically underserved. New projects have begun in collaboration with the Faculty of Medicine of the University of Mali, in Bamako, Mali to evaluate the CD4+ T cell responses to Mycobacterium tuberculosis in immune individuals and in individuals with active tuberculosis and HIV infection. New clinical research protocols were implemented in South Africa in collaboration with the South African National Defence Forces (SANDF), the United States Department of Defense, and the NIAID to evaluate the relative efficacy of several different antiretroviral regimens in persons associated with the SANDF who had not previously received antiretroviral therapy.